The proposed project will define those biochemical changes that are early, critical events in the onset of virus-induced leukemia by employing Gross virus given to normal C3H mice. Because lymphoid leukemia is a neoplastic proliferation of lymphoid cells and because cyclic Amp and cyclic GMP appear to be important in the proliferation of these cells, one might expect alterations in cyclic nucleotide metabolism during virus-induced neoplastic transformation. Preliminary results with leukemia in the AKR mouse indicate that such a change does occur. In the proposed study, to employ a more adequately controlled model for leukemogenesis, the activities and kinetic properties of adenylate cyclase and cyclic nucleotide phosphodiesterase will be measured in thymus cell preparation from mice injected with active Gross A virus and from mice treated with inactivated virus. Particular emphasis will be placed on analyzing those changes that occur in the preleukemic state. Changes in the levels of cyclic AMP and cyclic GMP in thymus lymphocytes in response to hormones and mitogens will be determined. The activities and isozyme distribution of serveral other representative soluble and membrane-bound enzymes will be examined during leukemogenesis to detemine whether changes in cyclic nucleotide metabolism are unique or are the result of general changes in the genetic expression of the cell. Alteration in energy metabolism during leukemogenesis will also be measured and a cause-effect relationship between changes in cyclic nucleotide metabolism and alterations in energy metabolism and cell proliferation will be sought. The study will hopefully provide a focal point for interfering with the chain of metabolic events that results in the virus-induced malignant evolution of lymphoid cells.